Bicyclic heterocycles as FGFR inhibitors

Abstract

The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR3 enzyme and are useful in the treatment of FGFR3-associated diseases such as cancer.

What is claimed is: 
     
       1. A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 Cy 1  is selected from:
 (i) phenyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; 
 (ii) 5-membered heteroaryl, wherein the 5-membered heteroaryl has at least one ring-forming carbon atom and 1, 2 or 3 ring-forming heteroatoms independently selected from O, S and N; wherein no more than 2 of the ring-forming heteroatoms of the 5-membered heteroaryl is N; wherein the N and S of the 5-membered heteroaryl are optionally oxidized; wherein a ring-forming carbon atom of the 5-membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 , 
 (iii) 6-membered heteroaryl, wherein the 6-membered heteroaryl has at least one ring-forming carbon atom, and 1, 2, or 3 ring-forming N atoms; wherein each N of the 6-membered heteroaryl is optionally oxidized; wherein a ring-forming carbon atom of the 6-membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 6-membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; 
 
 Cy A  is selected from 2,6-dimethylphenyl, 2-chloro-6-fluorophenyl, 2-chloro-6-methylphenyl, 2-methyl-6-(trifluoromethyl)phenyl, 4-fluoro-2,6-dimethylphenyl, 2-ethyl-6-methylphenyl, 2,6-diethylphenyl, 2-fluoro-6-methylphenyl, 2-methoxy-6-methylphenyl, 4-methoxy-2,6-dimethylphenyl, 4-cyano-2,6-dimethylphenyl, 2,6-dimethyl-4-(methylsulfonamido)phenyl, 4-acetamido-2,6-dimethylphenyl, and 4-(dimethylamino)-2,6-dimethylphenyl; 
 R 1  is selected from halo, CN, C 1-6  alkyl, C 3-4  cycloalkyl, azetidinyl, OR a  and NR c R d ; wherein the C 1-6  alkyl, C 3-4  cycloalkyl, and azetidinyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R g ; 
 each R 10  is independently selected from C 1-6  alkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ; 
 each R 11  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 3-10  cycloalkyl-C 1-3  alkylene, 4-10 membered heterocycloalkyl-C 1-3  alkylene, C 6-10  aryl-C 1-3  alkylene, 5-10 membered heteroaryl-C 1-3  alkylene, halo, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 3-10  cycloalkyl-C 1-3  alkylene, 4-10 membered heterocycloalkyl-C 1-3  alkylene, C 6-10  aryl-C 1-3  alkylene and 5-10 membered heteroaryl-C 1-3  alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R 12  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; wherein said C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R a , R c  and R d  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl, C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R a3 , R c3  and R d3 , is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 or any R c3  and R d3  attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R 12 ; 
 each R b3  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R a5 , R c5  and R d5 , is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl, C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 or any R c5  and R d5  attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R b5  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and 
 each R g  is independently selected from OH, NO 2 , CN, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-2  alkylene, C 1-6  alkoxy, C 1-6  haloalkoxy, C 1-3  alkoxy-C 1-3  alkyl, C 1-3  alkoxy-C 1-3  alkoxy, HO—C 1-3  alkoxy, HO—C 1-3  alkyl, cyano-C 1-3  alkyl, H 2 N—C 1-3  alkyl, amino, C 1-6  alkylamino, di(C 1-6  alkyl)amino, thio, C 1-6  alkylthio, C 1-6  alkylsulfinyl, C 1-6  alkylsulfonyl, carbamyl, C 1-6  alkylcarbamyl, di(C 1-6  alkyl)carbamyl, carboxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  alkylcarbonylamino, C 1-6  alkylsulfonylamino, aminosulfonyl, C 1-6  alkylaminosulfonyl, di(C 1-6  alkyl)aminosulfonyl, aminosulfonylamino, C 1-6  alkylaminosulfonylamino, di(C 1-6  alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6  alkylaminocarbonylamino, and di(C 1-6  alkyl)aminocarbonylamino. 
 
       
     
     
       2. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is 5 or 6-membered heteroaryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       3. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is 5-membered heteroaryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       4. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is pyrazolyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       5. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is 6-membered heteroaryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       6. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is pyridinyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       7. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is phenyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       8. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1  is selected from pyrazolyl, pyridinyl, and phenyl; each of which is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 . 
     
     
       9. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10  is independently selected from methyl, ethyl, propyl, cyclopropyl, cyclobutyl, piperazinyl, azetidinyl, piperidinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, and pyridinyl; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 . 
     
     
       10. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10  is independently selected from methyl, propyl, 2-hydroxyethyl, cyclopropyl, cyclobutyl, CH 2 C(O)NHCH 2 CH 3 , 4-acetylpiperazin-1-yl, 4-methylpiperazin-1-yl, 1-(dimethylcarbamoyl)azetidin-3-yl, 1-acetylpiperidin-4-yl, 4-methylpiperazin-1-yl, 1-(ethylcarbamoyl)azetidin-3-yl, 1-(methylsulfonyl)azetidin-3-yl, 1-acetylazetidin-3-yl, 1-methylpiperidin-4-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, pyridin-2-ylmethyl, piperidin-4-ylmethyl, 2-morpholinoethyl, pyridin-3-ylmethyl, pyridin-2-yl, 1-(ethoxycarbonyl)azetidin-3-yl, 1-(methoxycarbonyl)piperidin-4-yl, and 1-(methoxycarbonyl)azetidin-3-yl. 
     
     
       11. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10  is methyl. 
     
     
       12. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11  is independently selected from C 1-6  alkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, OR a3 , C(O)NR c3 R d3 , C(O)R b3 , C(O)OR a3 , and S(O) 2 R b3 . 
     
     
       13. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11  is C 1-6  alkyl. 
     
     
       14. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 12  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, CN, and OR a5 . 
     
     
       15. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from halo, C 1-6  alkyl, and OR a . 
     
     
       16. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from Cl, methyl, and methoxy. 
     
     
       17. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is methoxy. 
     
     
       18. The compound of  claim 1 , having Formula (IIa): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       19. The compound of  claim 1 , having Formula (IIb): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       20. The compound of  claim 1 , having Formula (IV): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       21. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 Cy 1  is 5-membered heteroaryl, wherein the 5-membered heteroaryl has at least one ring-forming carbon atom and 1, 2 or 3 ring-forming heteroatoms independently selected from O, S and N; wherein no more than 2 of the ring forming heteroatoms of the 5-membered heteroaryl is N; wherein each N and S of the 5-membered heteroaryl is optionally oxidized; wherein a ring-forming carbon atom of 5-membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; 
 R 1  is selected from halo, CN, C 1-6  alkyl, C 3-4  cycloalkyl, azetidinyl, OR a  and NR c R d ; wherein the C 1-6  alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ; 
 each R 10  is independently selected from C 1-6  alkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ; 
 each R 11  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 3-10  cycloalkyl-C 1-3  alkylene, 4-10 membered heterocycloalkyl-C 1-3  alkylene, C 6-10  aryl-C 1-3  alkylene, 5-10 membered heteroaryl-C 1-3  alkylene, halo, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3  NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, C 3-10  cycloalkyl-C 1-3  alkylene, 4-10 membered heterocycloalkyl-C 1-3  alkylene, C 6-10  aryl-C 1-3  alkylene and 5-10 membered heteroaryl-C 1-3  alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R 12  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; wherein said C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R a , R c  and R d  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl, C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 or any R c3  and R d3  attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R 12 ; 
 each R b3  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R a5 , R c5  and R d5  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl, C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 or any R c5  and R d5  attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R b5  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and 
 each R g  is independently selected from OH, NO 2 , CN, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-2  alkylene, C 1-6  alkoxy, C 1-6  haloalkoxy, C 1-3  alkoxy-C 1-3  alkyl, C 1-3  alkoxy-C 1-3  alkoxy, HO—C 1-3  alkoxy, HO—C 1-3  alkyl, cyano-C 1-3  alkyl, H 2 N—C 1-3  alkyl, amino, C 1-6  alkylamino, di(C 1-6  alkyl)amino, thio, C 1-6  alkylthio, C 1-6  alkylsulfinyl, C 1-6  alkylsulfonyl, carbamyl, C 1-6  alkylcarbamyl, di(C 1-6  alkyl)carbamyl, carboxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  alkylcarbonylamino, C 1-6  alkylsulfonylamino, aminosulfonyl, C 1-6  alkylaminosulfonyl, di(C 1-6  alkyl)aminosulfonyl, aminosulfonylamino, C 1-6  alkylaminosulfonylamino, di(C 1-6  alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6  alkylaminocarbonylamino, and di(C 1-6  alkyl)aminocarbonylamino. 
 
     
     
       22. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 Cy 1  is pyrazolyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; 
 R 1  is selected from halo, CN, C 1-3  alkyl, and OR a ; wherein the C 1-6  alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R g ; 
 each R 10  is independently selected from C 1-6  alkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ; 
 each R 11  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3  NR c3 C(O)OR a3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10  aryl, and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R 12  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, D, CN, OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , and S(O) 2 R b5 ; wherein said C 1-6  alkyl, is each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 R a  is selected from H, C 1-3  alkyl, and C 1-3  haloalkyl; 
 each R a3 , R c3  and R d3 , is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 or any R c3  and R d3  attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R 12 ; 
 each R b3  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ; 
 each R a5 , R c5  and R d5 , is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl, C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; 
 each R b5  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl and C 1-6  haloalkyl; wherein said C 1-6  alkyl C 2-6  alkenyl and C 2-6  alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and 
 each R g  is independently selected from OH, NO 2 , CN, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-2  alkylene, C 1-6  alkoxy, C 1-6  haloalkoxy, C 1-3  alkoxy-C 1-3  alkyl, C 1-3  alkoxy-C 1-3  alkoxy, HO—C 1-3  alkoxy, HO—C 1-3  alkyl, cyano-C 1-3  alkyl, H 2 N—C 1-3  alkyl, amino, C 1-6  alkylamino, di(C 1-6  alkyl)amino, thio, C 1-6  alkylthio, C 1-6  alkylsulfinyl, C 1-6  alkylsulfonyl, carbamyl, C 1-6  alkylcarbamyl, di(C 1-6  alkyl)carbamyl, carboxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  alkylcarbonylamino, C 1-6  alkylsulfonylamino, aminosulfonyl, C 1-6  alkylaminosulfonyl, di(C 1-6  alkyl)aminosulfonyl, aminosulfonylamino, C 1-6  alkylaminosulfonylamino, di(C 1-6  alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6  alkylaminocarbonylamino, and di(C 1-6  alkyl)aminocarbonylamino. 
 
     
     
       23. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 Cy 1  is pyrazolyl, pyridinyl, or phenyl, each of which is optionally substituted with R 10 ; 
 R 1  is selected from halo, C 1-3  alkyl, and OR a ; 
 each R 10  is independently selected from C 1-6  alkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; each of which is optionally substituted with R 11 ; 
 R 11  is independently selected from C 1-6  alkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, OR a3 , C(O)NR c3 R d3 , C(O)R b3 , C(O)OR a3 , and S(O) 2 R b3 ; 
 R a  is selected from H, C 1-3  alkyl, and C 1-3  haloalkyl; 
 each R a3 , R c3  and R d3  is independently selected from H, C 1-6  alkyl, and C 1-6  haloalkyl; and 
 each R b3  is independently selected from C 1-6  alkyl and C 1-6  haloalkyl. 
 
     
     
       24. The compound of  claim 1 , wherein the compound is selected from:
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-chloro-6-fluorophenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-chloro-6-methylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-6-(trifluoromethyl)phenyl)-1H-indazole-5-carboxamide; 
 N-(4-fluoro-2,6-dimethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-ethyl-6-methylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-diethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-fluoro-6-methylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-methoxy-N-(2-methoxy-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-methoxy-N-(4-methoxy-2,6-dimethylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(4-cyano-2,6-dimethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-chloro-N-(2,6-dimethylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-fluoro-6-methylphenyl)-6-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-chloro-N-(2-fluoro-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 6-chloro-N-(2-chloro-6-fluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2-chloro-6-fluorophenyl)-3-(1-cyclobutyl-1H-pyrazol-4-yl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2-chloro-6-fluorophenyl)-3-(1-cyclopropyl-1H-pyrazol-4-yl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-3-(1-(2-(ethylamino)-2-oxoethyl)-1H-pyrazol-4-yl)-6-methoxy-1H-indazole-5-carboxamide; 
 3-(4-(4-acetylpiperazin-1-yl)phenyl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indazole-5-carboxamide; 
 3-(1-(1-(dimethylcarbamoyl)azetidin-3-yl)-1H-pyrazol-4-yl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; 
 ethyl 3-(4-(5-((2,6-dimethylphenyl)carbamoyl)-6-methoxy-1H-indazol-3-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate; 
 methyl 4-(4-(5-((2,6-dimethylphenyl)carbamoyl)-6-methoxy-1H-indazol-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate; 
 3-(1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2, 6-dimethylphenyl)-6-methoxy-3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethyl-4-(methylsulfonamido)phenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(4-acetamido-2,6-dimethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(4-(dimethylamino)-2,6-dimethylphenyl)-6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-3-(1-(1-(ethylcarbamoyl)azetidin-3-yl)-1H-pyrazol-4-yl)-6-methoxy-1H-indazole-5-carboxamide; 
 methyl 3-(4-(5-((2,6-dimethylphenyl)carbamoyl)-6-methoxy-1H-indazol-3-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(1-(methylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 3-(1-(1-acetylazetidin-3-yl)-1H-pyrazol-4-yl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(pyridin-2-ylmethyl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-3-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-methoxy-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(pyridin-3-ylmethyl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide; 
 3-(1-cyclobutyl-1H-pyrazol-4-yl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; 
 3-(1-cyclopropyl-1H-pyrazol-4-yl)-N-(2,6-dimethylphenyl)-6-methoxy-1H-indazole-5-carboxamide; and 
 N-(2,6-dimethylphenyl)-6-methoxy-3-(1-propyl-1H-pyrazol-4-yl)-1H-indazole-5-carboxamide, 
 
       or a pharmaceutically acceptable salt of any of the aforementioned. 
     
     
       25. A pharmaceutical composition comprising a compound of  claim 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. 
     
     
       26. A method of inhibiting an FGFR3 enzyme comprising contacting said enzyme with a compound of  claim 1  or a pharmaceutically acceptable salt thereof.